This application is written in response to Request for Applications DA-06-002 entitled, "Pilot Clinical Trials of Pharmacotherapies for Substance Related Disorders." Cocaine abuse and dependence has been recognized as a significant public health problem, and no broadly effective medications are available. Recent promising results have been obtained from studies employing the agonist substitution or replacement approach, including studies of d-amphetamine and modafinil. This pilot project proposes to evaluate atomoxetine (Strattera), a compound presently marketed for the treatment of ADHD in adolescents and adults, for the treatment of cocaine dependence. Atomoxetine is a norepinephrine reuptake blocker, which has relatively low affinity for the dopamine and serotonin transport sites. It has been safely tolerated in clinical practice and is associated with low abuse potential. Preliminary data suggest that its pharmacodynamic effects overlap partially with prototypic stimulants, and that maintenance on atomoxetine can reduce the subjective response to cocaine and self-reported ratings of desire for cocaine in cocaine abusing volunteers. This application proposes to conduct a single, placebo-controlled, double blind, randomized pilot clinical trial to evaluate atomoxetine (Stattera) for the treatment of cocaine dependence. Cocaine-dependent healthy individuals, who are seeking treatment for their substance abuse, will be enrolled after careful medical and psychiatric screening to ensure their suitability for the study over a two- week period. Patients will be stratified on variables known to impact cocaine abuse treatment outcomes prior to randomization to one of two groups (n=25/group). Patients will be randomized to receive either atomoxetine (80 mg/day with a brief lead-in) or a matched-placebo during a trial lasting 12 weeks. All patients will participate in weekly cognitive behavioral counseling sessions. A contingency management procedure will be employed to reinforce attendance and decrease attrition from the trial. A broad array of measures, including measures of drug use, safety, mood, psychosocial functioning, and medication compliance (including riboflavin testing and pill counts) and cocaine craving will be collected throughout the course of the trial. The primary outcome measures will be urine toxicology results for benzoylecgonine over time and achievement of three consecutive weeks of abstinence. Secondary outcome measures will include clinic attendance, medication adherence, psychosocial functioning, and other drug use. Data will be analyzed using PROC Mix, General Estimating Equations and parametric ANOVA approaches. The group size was based upon power analyses derived from other trials in which positive medications signals were obtained in this population. This study will provide preliminary safety and efficacy data on the potential utility of atomoxetine and determine whether a larger-scale evaluation is warranted. [unreadable] [unreadable] [unreadable]